A large number of biologically active classes of natural products, among which are the harmila alkaloids, the ergolines, the mitomicins and many others derive biologically from the amino acid, tryptophan. The essential parent heterocyclic skeleton of all of these compounds is indole, a simple heteroaromatic compound isolated originally from coal tar. Indole derivatives, dimethyltryptamine, and reserpine. This study concentrates on syntheses of potentially active reagents related to indole but containing a sulfur atom. In Part I of the proposal, syntheses and testing of indole - cyclobutenes related, by a simple cyclobutene - butadiene ring opening to the benzodiazepines are proposed. Lipid solubility in these compounds can be controlled by structural modification in a rather general photochemical synthesis, thus the effect of polarity and stereochemistry on the activity of benzodiazepine precursors can be systematically studied. The compounds will be tested for pharmacological activity similar to that possessed by diazepam. A variety of animal test systems will be employed including behavior and motor performance in cats, dose response and lethality in mice, anticonvulsant activity and spinal reflux measurements.